Sarcoidosis

Synonyms of Sarcoidosis

Subdivisions of Sarcoidosis

General Discussion

Sarcoidosis is a multisystem disorder that most often affects individuals between 20 and 40 years of age. Females appear to be affected more frequently than males. Sarcoidosis is characterized by the abnormal formation of inflammatory masses or nodules (granulomas) consisting of certain granular white blood cells (modified macrophages or epithelioid cells) in certain organs of the body. The granulomas that are formed are thought to alter the normal structure of and, potentially, the normal functions of, the affected organ(s), causing symptoms associated with the particular body system(s) in question. In individuals with sarcoidosis, such granuloma formation most commonly affects the lungs. However, in many cases, the upper respiratory system, lymph nodes, skin, and/or eyes may be involved. In addition, in some cases, other organs may be affected, including the liver, bone marrow, spleen, musculoskeletal system, heart, salivary glands, and/or nervous system (i.e., central or peripheral nervous system).

The range and severity of symptoms associated with sarcoidosis vary greatly, depending upon the specific organ(s) involved and the degree of such involvement. In some cases, the symptoms of sarcoidosis may begin suddenly (acute), sometimes severely, and subside in a relatively short period of time (self limited). Acute sarcoidosis is often characterized by fatigue, fever, generalized muscle aches, difficulty breathing (dyspnea), joint pain, swollen glands, skin eruptions, eye irregularities, and/or other symptoms. In the subacute form, affected individuals may experience no symptoms (asymptomatic), even with organ involvement. In the chronic form of sarcoidosis, symptoms may appear slowly and subtly, and may persist or recur over a long time span. Initial symptoms of the chronic form of the disorder may include difficulty breathing (dyspnea), dry cough, limited airflow, and other respiratory abnormalities. Symptoms associated with other organ involvement may follow.

The exact cause of sarcoidosis is not known. However, possible infectious, environmental, genetic, and immunological factors are under investigation as potential causes of the disorder.

Signs & Symptoms

The manifestations of sarcoidosis are very broad, ranging from no symptoms to critical illness. They differ by ethnic group. Although sarcoidosis can present in any organ system, most patients have lung involvement with an abnormal chest x-ray. Symptoms from lung involvement may include dyspnea, cough, or chest pain.

Sarcoidosis is characterized by the abnormal formation of inflammatory masses or nodules (granulomas) consisting of granular white blood cells (modified macrophages or epithelioid cells) in certain organs of the body. Because such granuloma formation is thought to affect the normal structure and functions of the affected organ(s), associated symptoms vary, depending upon the specific organ(s) involved and the degree of such involvement. The symptoms and physical findings associated with sarcoidosis may reflect the involvement of a single organ system or multisystem disease.

In most individuals with sarcoidosis, granuloma formation affects the lungs. However, in many cases, the upper respiratory system, lymph nodes, skin, and/or eyes may be involved. In some cases, other organs may be affected including the liver, bone marrow, spleen, musculoskeletal system, heart, salivary glands, and/or nervous system (i.e., central or peripheral nervous system).

Most individuals with the acute form of sarcoidosis develop symptoms over a period of weeks. These symptoms may include unusual fatigue, unexplained fevers, loss of appetite (anorexia), and/or a general feeling of discomfort and ill health (malaise). Some affected individuals may also experience a dry cough, difficulty breathing (dyspnea), chest (retrosternal) discomfort, and/or other symptoms and findings.

Lofgren’s Syndrome, an acute form of sarcoidosis, generally describes a certain combination of symptoms and findings including the development of tender, red, inflamed nodules (erythema nodosum) on both legs (bilateral); pain in several joints (polyarthralgia); and enlargement of the lymph glands located where the blood vessels enter and exit the lungs (bilateral hilar lymphadenopathy or adenopathy). (Such lymph gland enlargement may be detected by chest x-ray.) It affects individuals of northern European descent and is usually self-limited.

Heerferdt-Waldenstrom Syndrome, also an acute form of sarcoidosis, describes another specific combination of symptoms and findings that includes fevers, enlargement of the salivary glands located near the ears (parotid glands), inflammation of the front portion of the middle layer of the eyes (anterior uveitis), and paralysis (palsy) of the facial nerve.

Many individuals with subacute sarcoidosis may experience no apparent symptoms (asymptomatic). In such cases, the disorder may be discovered during a routine chest x-ray in which lymph node and/or lung involvement may be evident.

In some individuals with sarcoidosis, symptoms develop gradually and subtly over a period of months. Initially, such individuals may experience respiratory difficulties that are most often associated with lung involvement. In some cases, other organ systems may eventually become involved. This type of onset is often suggestive of the development of the chronic form of sarcoidosis.

According to some reports, up to two thirds of individuals with sarcoidosis may have acute or subacute disease with a “self-limiting” course, experiencing spontaneous remissions. However, in about 10 to 33 percent of affected individuals, the disease may tend to be chronic and progressive, potentially following a waxing and waning course over many years. In individuals with the acute, subacute, or chronic form of sarcoidosis, many different organs or organ systems may be affected (multisystemic). The range and severity of symptoms associated with the disorder vary greatly depending on the organ(s) or organ system(s) involved. At diagnosis, as many as seven percent may have serious disease involvement outside the lungs (extrapulmonary disease), such as of the liver, heart, and/or brain and spinal cord (central nervous system). With chronic disease progression, a greater percentage of affected individuals may develop extrapulmonary involvement.

Lungs and Upper Respiratory System

Approximately 90 percent of individuals with sarcoidosis experience some degree of lung involvement. Some may have no apparent symptoms, whereas others may experience severe associated abnormalities. The air sacs (alveoli), the small airways (bronchioles), and the small blood vessels of the lungs are often affected, resulting in difficulty breathing (dyspnea), particularly after exercise or exertion; a dry cough; and/or a small hissing or whistling sound (dry rales) from the lungs that may be heard by an examining physician with a stethoscope. In rare instances, sudden, severe coughing episodes may produce vomiting. In some cases, the presence of inflammatory masses or nodules (epithelioid granulomas) within the major air passages (bronchi) may produce asthma-like symptoms including wheezing; abnormal, high-pitched sounds heard upon inhalation (stridor); limited airflow; and/or irregularities in the oxygen/carbon dioxide exchange within the lungs. In addition, in some cases, a portion of the lung may collapse or fail to expand completely (atelectasis). Occasionally, the membrane that surrounds the lungs (pleura) may become inflamed (pleuritis). In addition, fluid may accumulate abnormally on one side of the chest cavity (pleural effusion). Although this condition may last only a few weeks, permanent thickening of the pleura may result. In a small percentage of cases, fibrous tissue (fibrosis) replaces normal tissue and there is permanent scarring of the lung(s).

In approximately 20 percent of individuals with sarcoidosis, the mucous membranes lining the nose (nasal mucosa) may be involved, usually resulting in nasal congestion. Additional areas of the upper respiratory system may also be affected such as the tonsils, the enlarged upper portion of the trachea (larynx), the structure that covers the entrance of the larynx when swallowing (epiglottis), and/or the area around the vocal cords. Associated symptoms may include hoarseness, difficulty breathing (dyspnea), wheezing, or, in rare cases, limitation of airflow or complete obstruction of the upper respiratory tract.

Lymph Nodes

Approximately 75 to 90 percent of individuals with sarcoidosis have enlarged lymph nodes in the chest cavity (intrathoracic). Lymph nodes are often affected on both sides of the chest (bilateral). In many cases, lymph nodes that are located where the blood vessels enter and exit the lungs (hilar lymphadenopathy or adenopathy) are involved. In addition, in some cases, lymph nodes located near the windpipe (paratracheal) and/or other lymph nodes in the chest (intrathoracic nodes) may also be affected. In addition, painless swelling may occur in lymph nodes directly under the skin (peripheral lymph nodes) including those in the neck (cervical), armpits (axillary), and/or groin (inguinal). Lymph gland enlargement usually does not present problems except when excessively swollen nodes intrude upon other body organs or blood vessels.

Skin and Subcutaneous Tissue

Skin lesions occur in approximately 25 percent of affected individuals. Such lesions may include tender, red, inflamed nodules (erythema nodosum) on both legs; purplish, elevated, painless patches (plaques), usually on the face; and/or a combination of small, flat, discolored spots (macules) and solid, waxy-topped bumps (papules) on the face, buttocks, arms, and/or legs. In addition, some affected individuals may have small painless nodules under the skin (subcutaneous) of the trunk, arms, legs, and/or other areas.

Lupus pernio, a less common skin abnormality associated with sarcoidosis, is characterized by hardened (indurated), violet-colored nodules and patches (plaques) on the nose, cheeks, ears, lips, fingers, hands, and/or knees. In some cases, these lesions may invade underlying bone and cartilage, particularly of the nasal passages, sometimes resulting in disfigurement. (Lupus pernio occurs more often in older females and in individuals of West Indian or African descent.)

Some individuals with sarcoidosis may also experience inflammation in old scars and/or tattoos. This inflammatory process may produce reddish-violet lesions that eventually fade to a brownish color. Scarring from erythema nodosum or earlier biopsies and/or sites used for inoculation or skin testing are also susceptible to this inflammatory involvement. In addition, in some affected individuals, the tips of the fingers may be abnormally enlarged and fleshy (clubbed) with skin that appears chafed or rough. Clubbing of the fingertips is often associated with chronic fibrosis of the lungs.

Eyes

Eye abnormalities affect approximately 25 percent of individuals with sarcoidosis. The most common of these is inflammation of all or part of the front middle portion of the eye (anterior uveitis) (including the colored portion [iris], the membrane covering the back portion [choroid], and the portion that joins the iris and choroid [ciliary body]). Symptoms associated with anterior uveitis may include excessive tearing, blurry vision, and/or abnormal sensitivity to light (photophobia). Anterior uveitis may appear in an acute form, with spontaneous healing within 12 months, or in a chronic form of longer duration. In some cases, uveitis may cause additional complications such as increased fluid pressure within the eyes (glaucoma); loss of transparency of the lens of the eyes (cataracts); adhesion of the iris to the lens or the clear portion of the eyes through which light passes (iris synechiae); and/or visual impairment or blindness.

Some individuals with sarcoidosis may also have abnormalities of the mucous membranes that line the eyelids (conjunctiva), including the formation of small, slightly elevated nodules that may appear cloudy (opaque) and/or gray or yellow. In addition, affected individuals may experience involvement of the glands that secrete tears (lacrimal glands), sometimes resulting in corneal irritation accompanied by dry, sore, burning, itchy, and/or “gritty-feeling” eyes (keratoconjunctivitis sicca).

Liver

In approximately 75 percent of individuals with sarcoidosis, epithelioid granulomas may develop in the liver. However, only 20 percent of such affected individuals may experience enlargement of the liver (hepatomegaly). In such cases, symptoms may include intense itching (pruritis) and/or, less commonly, fevers. In rare cases, the flow of certain liver secretions (bile) may be interrupted or stopped (cholestasis) and fibrous tissue may abnormally accumulate in the liver (cirrhosis), resulting in abnormal liver function.

Bone Marrow and Spleen

Approximately 15 to 40 percent of individuals with sarcoidosis experience bone marrow involvement. In such cases, although some individuals may not experience associated findings, others may exhibit slightly decreased levels of the oxygen-carrying portion (hemoglobin) of red blood cells (anemia), abnormally low levels of circulating blood platelets (thrombocytopenia), decreased numbers of certain white blood cells (neutropenia), and/or an increase in another type of white blood cells called eosinophils (eosinophilia).

In addition, in approximately 50 to 60 percent of affected individuals, granulomas may develop in the spleen. However, only about 10 to 30 percent of such individuals experience enlargement of the spleen (splenomegaly). On rare occasions, spleen involvement may result in a decrease in the white blood cell count (leukopenia) and/or a drop in the number of circulating blood platelets (thrombocytopenia), possibly resulting in small hemorrhages within skin (dermal) layers or layers below the mucous membranes (submucosal) and increased susceptibility to bruising (thrombocytopenic purpura).

Musculoskeletal System

Approximately 25 to 50 percent of individuals with sarcoidosis experience pain as well as swelling and inflammation of the joints (arthralgia or polyarthralgia, arthritis), particularly the large joints. Such joint pain, swelling, and inflammation occurring in association with erythema nodosum (as in Lofgren’s Syndrome) may be severe but is often of short duration. In some cases, however, chronic polyarthralgias may develop along with a thickening of the fluid that lubricates the joints (synovial fluid). Joint pain may recur and is often accompanied by additional skin and bone changes.

According to the medical literature, approximately five to eight percent of affected individuals experience bone changes (e.g., the development of cysts of various sizes), particularly in the small bones of the hands and feet. Affected areas may be swollen and tender to the touch, and changes in the skin overlying the affected sites may also be apparent.

In addition, although an estimated 50 to 80 percent of individuals with sarcoidosis have granulomatous involvement of muscle tissue, associated muscular dysfunction seldomly occurs. In rare cases, however, muscle inflammation (polymyositis) and/or muscle weakness may be present. Elderly females may be particularly susceptible to muscle weakness.

Heart

Approximately five to 10 percent of individuals with sarcoidosis develop significant cardiac abnormalities. These may include irregularities of the electrical impulses (signals) that coordinate the heart’s muscular contractions (electrocardiographic conduction defects) accompanied by an increased heart rate (tachyarrhythmia) and/or enlargement of the heart (cardiomegaly or myocardiopathy). Affected individuals may also experience inflammation of the membrane (pericardium) surrounding the heart (pericarditis); abnormalities of the valve(s) of the heart; and/or reduced function of the left lower chamber of the heart (ventricle). In addition, chronic involvement of the lungs may result in and/or contribute to cardiac complications including abnormally high blood pressure within the pulmonary circulation (pulmonary hypertension) and/or enlargement (hypertrophy) of the right ventricle of the heart (chronic cor pulmonale). Due to such cardiac and lung function abnormalities, affected individuals may experience an inability of the heart to pump blood effectively throughout the body (congestive heart failure), breathlessness, lightheadedness, fainting spells upon exertion, fatigue, fever, chest pain, and/or other associated symptoms and findings.

Salivary Glands

Approximately 10 percent of individuals with sarcoidosis experience enlargement of the salivary glands near the ears (parotid glands). In most cases, both sides of the face are affected (bilateral). The swelling is typically painless, and the affected glands are smooth and hard to the touch. In addition, dryness of the mouth (xerostomia) often occurs. Less frequently, paralysis (palsy) of the facial nerve may accompany the enlargement of the parotid glands.

Nervous System

Approximately five percent of affected individuals experience granulomatous involvement of the nervous system. Any portion of the nervous system may be affected (i.e., central or peripheral nervous system). The most common finding in such cases is involvement of the seventh cranial nerve, resulting in sudden, usually temporary, one-sided (unilateral) facial paralysis (palsy). However, any of the 12 nerve pairs that arise from the brain (cranial nerves) may be affected. For example, in some cases, swallowing difficulties and/or hearing impairment may occur in association with cranial nerve involvement. Affected individuals may also experience inflammation of the cranial nerve that transmits impulses from the nerve-rich membrane lining the eyes (retina) to the brain (optic nerve), potentially causing pain upon moving the eye and sudden loss of part of the visual field, which typically improves with time.

In addition, in some individuals with sarcoidosis, nervous system involvement may cause mild inflammation of the membranes (meninges) surrounding the brain and spinal cord (meningitis), potentially resulting in such symptoms as headache, fever, nausea, and/or stiffness of the neck. Some affected individuals may experience hydrocephalus, a condition characterized by inhibition of the normal flow of cerebrospinal fluid (CSF) and abnormal widening (dilatation) of the cerebral spaces of the brain (ventricles), causing accumulation of CSF in the skull and potentially increased pressure on the brain. Associated symptoms and findings may include headache; swelling of the optic disk (papilledema), the portion of the optic nerve that enters the eye and joins with the retina; and/or impaired muscle coordination. Some affected individuals with nervous system involvement may also experience impaired transmission of certain nerve impulses due to disturbances of nerves outside the brain and spinal cord (peripheral neuropathy). Associated symptoms depend upon which peripheral nerves (e.g., motor or sensory nerve fibers) are affected. Motor nerve involvement may be characterized by progressive muscle thinning and weakness, whereas sensory nerve involvement may cause tingling, numbness, and abnormal sensations of pain or cold.

According to the medical literature, some affected individuals with nervous system involvement may also experience episodes of uncontrolled electrical disturbances in the brain (seizures); abnormal emotional, behavioral, and/or mental changes (psychiatric abnormalities); and/or other symptoms and findings.

Other Symptoms

Some scientists believe that the granulomas associated with sarcoidosis may produce 1,25-dihydroxyvitamin D, a hormone that increases intestinal absorption of calcium, resulting in an excessive amount of calcium in the blood (hypercalcemia) and in the urine (hypercalcuria). Symptoms associated with hypercalcemia may include nausea, lack of appetite (anorexia), fatigue, abdominal pain, muscle pain, weakness, and/or confusion. Mild, chronic hypercalcemia and hypercalcuria may result in the formation of kidney stones (nephrolithiasis) or calcium deposits in the tissues of the kidneys (nephrocalcinosis). Kidney stones may cause intense pain that comes and goes in waves (fluctuates) or less severe, more constant pain, depending upon the exact location of the stones. Other associated symptoms and findings may include chills, fever, nausea, vomiting, traces of blood in the urine (hematuria), an inability to urinate (anuria), and/or swelling (distention) of the abdomen. Nephrocalcinosis may result in hematuria, infection, and, in some cases, decreased or insufficient kidney function.

Granulomatous involvement of some glands that produce internal secretions (endocrine glands) may result in such abnormalities as diabetes insipidus, an irregularity of metabolism characterized by excessive urination (polyuria) and excessive thirst (polydipsia). (For more information on this disorder, choose “diabetes insipidus” as your search term in the Rare Disease Database.)

In addition, reports in the literature have indicated sarcoid granuloma involvement in almost every other organ of the body, often producing no significant accompanying symptoms.

Causes

The exact cause of sarcoidosis is not known. Possible infectious, environmental, genetic, and immunological factors are under investigation as potential causes of sarcoidosis.

Some studies suggest that person-to-person transmission of specific bacterial (e.g., mycobacterial), viral, or fungal infection or exposure to certain environmental factors (e.g., metal dusts or organic antigens) acquired through ingestion, inhalation, and/or skin contact may play a role in causing the disorder. Many scientists stress the potential role of specific environmental agents as evidenced by the appearance of clusters of affected individuals, both related and unrelated, within the same work or home community.

Researchers also theorize that affected individuals may carry genes for or genetic susceptibility to sarcoidosis. However, it is suspected that the disease gene(s) may not be expressed unless something in the environment triggers the disease (multifactorial). Researchers indicate that such genetic predisposition may be evidenced by the similarity of symptoms and organ involvement within certain ethnic groups. (For example, Lofgren’s Syndrome is the most common form of the disorder in females of Swedish, Irish, and Puerto Rican descent. In addition, affected individuals of West Indian descent who live in London most often have the chronic form of sarcoidosis.)

In individuals with sarcoidosis, particular components of the immune system, which is responsible for defending the body against foreign agents (e.g., toxins; microorganisms including bacteria and viruses; etc.), may respond inappropriately to the presence of certain agents (antigens). Due to inappropriately heightened immune responses, there is an abnormal proliferation of certain white blood cells (macrophages) that serve to surround and destroy microorganisms, cellular debris, and foreign particles (phagocytosis). The abnormal proliferation of macrophages in affected tissue(s) results in the formation of the inflammatory masses or nodules (epithelioid granulomas) associated with sarcoidosis. Researchers suspect that the enhanced immune responses occurring in sarcoidosis do not, in and of themselves, damage affected organs. Rather, the epithelioid granulomas that are formed as a result of these processes accumulate in certain tissues and affect the normal structure of the affected organ(s). (That is, the granulomas actually replace normal organ tissue (parenchyma]). Significant “stuctural involvement” may interfere with the normal functions of the affected organ(s), causing symptoms associated with the particular body system(s) in question.

Affected Populations

Sarcoidosis appears to affect females slightly more frequently than males. Symptom onset usually occurs in individuals aged 20 to 40 years, particularly between the ages of 20 and 29. In Japan, women over the age of 50 are frequently affected, as well. Less commonly, the disorder may become apparent in children, adolescents, or elderly individuals.

Sarcoidosis has been observed worldwide, affecting people in many ethnic and geographic populations. According to some reports, the disorder appears to be most frequent in moderate (temperate) climates. In the United States, more African-Americans than Caucasians are affected by sarcoidosis, with an estimated incidence rate of 35.5 individuals of African descent per 100,000 and 10.9 Caucasians per 100,000 annually. Some researchers have suggested that, in the U.S., individuals of African descent have a higher incidence of the disease than Caucasians by a ratio of approximately 10 to one; however, more recent studies indicate a lower ratio. In addition, evidence suggests that the disorder may tend to be more severe in individuals of African descent, whereas Caucasians may be more likely to have no associated symptoms (asymptomatic).

It is important to note that estimates concerning the numbers of individuals with sarcoidosis may not reflect the true frequency of the disorder in the general population. This may be due to the extreme variability in symptom range and severity, the lack of apparent symptoms in some individuals, and the fact that some may consequently remain undiagnosed. In addition, a high incidence of reported cases in certain regions or countries may be a result of more frequent testing, as may be suggested by the relatively high number of affected school children in Japan, where routine chest x-ray screening is performed.

Additionally, researchers have described familial cases of the disorder among individuals within several hundred families (kindreds). Sarcoidosis has also been reported among husbands and wives and in other unrelated individuals who live or work in close proximity. Such observations give credence to the belief that genetic predisposition and/or environmental factors may play a role in some cases of sarcoidosis.

Related Disorders

Symptoms of the following disorders may be similar to those of sarcoidosis. Comparisons may be useful for a differential diagnosis:

Lymphoma is an abnormal growth of lymphoid tissue, frequently malignant, that often first appears as an enlarged lymph node(s) in the neck, groin, armpit, and/or other area. Initial symptoms may include generalized weakness, fever, weight loss, and/or decreased levels of the oxygen-carrying portion (hemoglobin) of red blood cells (anemia). There are many different types of lymphomas, each with its own name and unique characteristics. (For more information on these disorders, choose “Lymphoma” as your search term in the Rare Disease Database.)

Tuberculosis (TB) is an acute or chronic bacterial infection most commonly found in the lungs, although the kidneys, bones, lymph nodes, and/or membranes surrounding the brain (meninges) may also be affected. In some cases, this infection may spread throughout the body. Tuberculosis is transmitted by the inhalation or ingestion of droplets breathed or coughed into the air by individuals infected with the bacteria that causes TB (Mycobacterium tuberculosis). This bacteria then causes the formation of tubercles (granulomas) in affected organs, often resulting in breathing difficulties, fever, loss of appetite, weight loss, weakness, and/or a dry cough. In some cases of advanced lung involvement, blood may appear in the sputum. The elderly and individuals with suppressed immune systems, such as those with AIDS or who have undergone organ transplantation and are taking immune suppressive drugs, are at increased risk from exposure to tuberculosis. There are many different subtypes of tuberculosis, each with its own characteristics. (For more information on this disorder, choose “Tuberculosis” as your search term in the Rare Disease Database.)

Leprosy is a progressive chronic infectious disease caused by the bacteria Mycobacterium leprae. This disease, which is rare in the United States yet is prevalent in third world countries, affects the nerves that are located outside the central nervous system (peripheral nerves), the skin, and/or other tissues of the body. Symptoms associated with peripheral nerve involvement may include burning and/or tingling sensations (paresthesias), lack of feeling in the affected areas (anesthesia), weakness, paralysis, and/or loss of muscle tissue (atrophy). In addition, skin lesions, including flat, spotty discolorations (macules); raised areas of red skin (papules); small nodules; and/or raised discolorations (plaques) may occur along the area where nerves are grouped together (nerve trunks). Complications that may arise from severe bacterial involvement include eye inflammations and/or abnormalities and deformities of the face, hands, and/or feet. Other complications may include high fever, decay (necrosis) of skin nodules, and/or pain resulting from nerve inflammation (Erythema Nodosum Leprosum or ENL). Although the mode of transmission is not fully understood, many researchers believe that leprosy is transmitted through direct skin contact, sexual contact, or inhalation. (For more information on this disorder, choose “Leprosy” as your search term in the Rare Disease Database.)

Histoplasmosis, an infection caused by the inhalation or ingestion of spores of the fungus Histoplasma capsulatum, is seen worldwide but is most prevalent in the midwestern United States. In some cases, there are few, if any, noticeable symptoms. In other cases, affected individuals may experience fever, generalized discomfort and fatigue (malaise), cough, and/or swollen lymph glands (lymphadenopathy). Additional symptoms may include the appearance of tender, red inflamed nodules (erythema nodosum) and/or pain and swelling in the joints (arthralgia or polyarthralgia). Most symptoms subside spontaneously; however, in some cases, small deposits of calcium salts (calcifications) may be left behind in the lungs and/or affected lymph glands. A more severe form of this infection (progressive histoplasmosis) in which the bacteria is scattered (disseminated) from the lungs to other parts of the body is characterized by severe and extensive involvement of the lungs, open sores in the mouth and/or nose, enlargement of the liver and spleen (hepatosplenomegaly), enlarged lymph nodes (lymphadenopathy), inflammation of the membranes covering the brain and spinal cord (meningitis), and/or other symptoms associated with affected organs.

Berylliosis is a poisoning caused by inhalation of the dust or fumes of beryllium or its compounds. Beryllium is a metallic element often found in alloys and fluorescent powders and is often used in occupational settings, particularly in the aerospace and nuclear power industries. In some cases, workers may bring home contaminated dust on their clothes, possibly exposing their families to beryllium poisoning. Some individuals may not exhibit symptoms of berylliosis for as many as 20 years after initial exposure to beryllium. Inhalation of or, in some cases, exposure to beryllium through the skin may result in the formation of granulomas in the lungs and/or throughout the body. Acute berylliosis primarily affects the lungs and may result in a dry cough, nasal discharge, and/or sore throat. In addition, affected individuals may experience weight loss, joint pain, and/or unexplained fatigue. An allergic reaction to beryllium may be characterized by the appearance of reddened patches or small, raised, discolored spots on the face, neck, arms, and/or hands. In some cases, lymph nodes near the affected areas of the skin may become enlarged. With prolonged exposure, this disorder may become chronic and may be characterized by a bluish tinge to the skin (cyanosis), fever, and/or weight loss. In addition, breathing may become progressively more difficult, particularly when lying down. Other symptoms may include those associated with abnormalities of the heart and/or eyes. (For more information on this disorder, choose “Berylliosis” as your search term in the Rare Disease Database.)

Sjogren Syndrome is an autoimmune disorder characterized by degeneration of the mucous-secreting glands, particularly those that produce tears (lacrimal glands) and the salivary glands, resulting in decreased tear and saliva production. In addition, decreased saliva production and subsequent dryness of the mouth (xerostomia) may result in difficulties with chewing and swallowing, causing food debris to stick to the cheeks, gums, and/or throat. This may increase the risk of tooth decay (dental caries), inflammation of the gums (gingivitis), and/or advanced gum disease (pyorrhea). Symptoms that may arise from decreased tear production include grittiness, burning, and/or itching of the eyes. In some cases, the eyelids may stick together and the cornea and delicate membrane lining the eyelids (conjunctiva) may become inflamed (keratoconjunctivitis). Other symptoms of this disorder may include dryness of the skin and mucous membranes and/or muscle weakness and pain (fibromyalgia). Although the exact cause of Sjogren Syndrome is unknown, researchers believe that many affected individuals carry a gene for this disorder that is not expressed until triggered by something in the environment (genetic predisposition). (For more information on this disorder, choose “Sjogren” as your search term in the Rare Disease Database.)

There may be additional disorders characterized by the formation of granulomas and associated symptoms and findings similar to those of sarcoidosis. (For more information on these disorders, choose “granuloma” as your search term in the Rare Disease Database.)

Diagnosis

The diagnosis of sarcoidosis is often difficult in that many associated symptoms and clinical findings are similar to those seen in individuals with other disorders. To establish a definite diagnosis, it is essential that each finding be evaluated in the context of all other findings. In addition, exclusion through differential diagnosis is an important aspect in the identification of this disorder. For example, in comparing granulomas of sarcoidosis with those associated with tuberculosis, microscopic examination may show subtle differences within the cellular components of the granulomas. Also, when the tissues of tuberculosis granulomas degenerate, they are converted into a dry, cheese-like, shapeless mass (caseate). In contrast, the appearance of sarcoidosis granulomatous tissue undergoes only subtle changes.

According to physicians who specialize in the care of individuals with sarcoidosis, the overall diagnostic assessment should include the removal (biopsy) and microscopic examination of tissue samples to confirm certain abnormalities of cellular growth and composition (histology); disease staging; and necessary evaluations to determine the extent of specific organ involvement, the risk of disease progression, and treatment measures that may be of benefit.

More specifically, diagnostic measures typically include a thorough medical history with a review of all previous laboratory test results and chest x-rays, an environmental and occupational history, physical examination, specialized tests, and, as mentioned above, the surgical removal and microscopic examination of tissue samples to confirm the presence of the typical granulomas associated with sarcoidosis. Such tissue samples may be obtained by a small incision in the most accessible affected organ.

Because most affected individuals have pulmonary involvement, disease staging often includes chest x-ray imaging. Chest x-rays may detect involvement of the lungs and lymph nodes in the chest (intrathoracic) and allow appropriate disease classification into one of four stages: Stage 0 — no involvement of the lungs or intrathoracic lymph nodes; Stage 1 — bilateral hilar lymphadenopathy; Stage 2 — bilateral hilar lymphadenopathy with involvement of the functioning aspects of the lung or lung tissue (parenchyma); or Stage 3 — late stage of lung involvement with formation of fibrous tissue (fibrosis) and pulmonary insufficiency.

Other pulmonary diagnostic tests may include bronchoalveolar lavage (BAL), in which a long, narrow tube with a light on the end (bronchoscope) is directed down through the windpipe (trachea) to the large air passages (bronchi) while the individual is sedated. A sterile saline solution is pumped in through the bronchoscope and, upon removal, the cells that have been washed out (lavaged) are analyzed for immune activity. In addition, a number of pulmonary function tests may be used to determine how efficiently the lungs are performing their functions.

Cardiac irregularities may be detected through specialized testing that records the electrical activities of the heart muscle (electrocardiogram or EKG). In addition, evaluation of eye (ophthalmic) involvement may be accomplished with a slit lamp, an instrument that projects a high-intensity beam of light through a narrow slit onto the interior of the eye, allowing examination of this illuminated portion through a magnifying lens.

Although there is no blood test that is definitive for sarcoidosis, blood tests may be helpful in measuring and analyzing cell counts, cell function, blood proteins, calcium levels, and/or liver function. In addition, a substance called angiotensin-converting enzyme (ACE), secreted by the cells of sarcoidosis granulomas, may sometimes be detected through blood testing of affected persons. It is important to note that results from blood tests must be observed in conjunction with all other diagnostic tests and measures, for levels indicative of sarcoidosis may also be indicative of other disorders.

To aid in determining the extent of organ involvement, physicians may suggest gallium scanning, a test during which an affected individual is injected with the radioactive chemical element gallium-67. After waiting approximately two days, the affected individual is then examined by advanced imaging scanning. Because gallium may collect at any active site of inflammation, scanning will detect this “uptake” and thus indicate what areas are inflamed and to what extent. However, gallium scanning cannot detect a cause for the inflammation. For this reason, a positive test is not necessarily indicative of sarcoidosis.

Other diagnostic testing specific to particular organs may also be performed, depending on presentation of symptoms, evaluation of chemical information, and/or other factors.

Standard Therapies

Treatment

Treatment of sarcoidosis requires the coordinated efforts of a team of specialists who may need to work together to systematically and comprehensively plan an affected individual's treatment. Such specialists may include internists; physicians who diagnose and treat disorders of the lungs (pulmonologists); dermatologists; eye specialists (ophthalmologists); physicians who diagnose and treat inflammatory disorders of the joints, muscles, and related structures (rheumatologists); neurologists; physicians who diagnose and treat abnormalities of the heart (cardiologists); and/or other health care professionals.

According to some reports, up to two thirds of individuals with sarcoidosis may experience spontaneous remissions, depending upon disease stage and/or other factors. Therefore, the first line of defense may be simply that of observation with periodic evaluation. For those individuals who experience a worsening of symptoms, who have severe organ involvement, or who have progressive disease, treatment with oral corticosteroids (i.e., prednisone) may be instituted. For example, oral corticosteroid therapy is indicated for individuals with certain abnormalities such as unusually increased levels of calcium in the blood (hypercalcemia), associated heart disease, and neurologic involvement. Because of the potential side effects of long-term corticosteroid therapy, physicians work closely with affected individuals to establish the minimum dose that may maintain remission. If symptoms recur after the course of medication is completed, another course of medication may be indicated. When warranted, certain drugs that reduce activities of the body's immune system (immunosuppressant agents), such as methotrexate or azathioprine, may be used in conjunction with prednisone or alone to help suppress associated symptoms.

Corticosteroid ointments or drops are sometimes effective in treating eye inflammations that may develop in the forward portion of the eye, whereas deep-seated inflammatory activity may require oral medication. In addition, in those individuals whose involvement is mainly limited to skin eruptions where oral treatment is not indicated, topical application of steroid ointment or cream may prove beneficial.

Other treatment is symptomatic and supportive and is directed toward those symptoms that may most impact the activities and general well-being of each individual.

Investigational Therapies

If you are experiencing symptoms of chronic sarcoidosis despite your current therapy, you may be interested in learning more about a clinical research study that is being conducted to evaluate two investigational drugs for chronic sarcoidosis. You may be eligible to participate if you are 18 to 85 years of age, have been told by your doctor that you have chronic sarcoidosis with lung and/or skin involvement, are experiencing symptoms despite your current therapy. Study volunteers will be provided research related medical care and medication at no cost. To learn more about this research study, please visit ClinicalTrials.gov identifier: NCT00955279

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

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If you are seeking information about a rare disease that is not in this database, we would suggest contacting the Genetic and Rare Diseases Information Center (GARD) at the National Institutes of Health. NIH has the most complete database of rare diseases in the U.S.

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